Understanding the mechanisms of human pluripotent stem cells (hPSCs) specification, development and differentiation to gametes are useful for elucidating the causes of infertility and potential treatment. This study aims to examine whether hPSCs can be induced to DDX4 extracellularly expressing primordial germ cell-like cells (DDX4 PGCLCs) and further into ovarian follicle stage in a combined and model. The transcriptional signatures show that these DDX4 PGCLCs are characteristic of PGCs and express ovarian folliculogenesis markers. We also verify that keratin (KRT)-8 is highly expressed in the DDX4 PGCLCs and plays a crucial role in germ cell migration. By co-culturing DDX4 PGCLCs with human granulosa cells (GCs), these cells are further induced into ovarian follicle-like structures in a xenograft mice model. This approach can in the future design practical strategies for treating germ cell-associated issues of infertility.
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http://dx.doi.org/10.1016/j.isci.2020.102003 | DOI Listing |
Cells
November 2022
Laboratoire de Développement des Gonades, UMRE008 Stabilité Génétique Cellules Souches et Radiations, Université Paris Cité, Université Paris-Saclay, CEA, 92265 Fontenay-aux-Roses, France.
The generation of oocytes from induced pluripotent stem cells (iPSCs) was proven efficient with mouse cells. However, no human iPSCs have yet been reported to generate cells able to complete oogenesis. Additionally, efficient sorting of human Primordial Germ Cell- Cells (hPGC-LCs) without genomic integration of fluorescent reporter for their downstream manipulation is still lacking.
View Article and Find Full Text PDFiScience
January 2021
Department of Obstetrics and Gynecology, College of Medicine and the Hospital, National Taiwan University, Taipei, Taiwan.
Stem Cell Res Ther
March 2020
School of Basic Medical Sciences, Wuhan University, 115 Donghu Road, Wuhan, 430071, China.
Background: In mammals, specification of primordial germ cells (PGCs) is established in the early post-implantation embryo. The bone morphogenetic protein (BMP)-SMAD and WNT3-β-catenin signaling initiate the gene regulatory network for PGC specification. The activation of SOX17-BLIMP1 axis is critical for human PGC program.
View Article and Find Full Text PDFMol Hum Reprod
May 2015
Department for Reproductive Medicine, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
Human embryonic stem cells (hESCs) derived in the presence of Activin A (ActA) demonstrate an increased differentiation propensity toward the germ cell lineage. In addition, mouse epiblast stem cells and mouse epiblast-like cells are poised toward germ cell differentiation and are derived in the presence of ActA. We therefore investigated whether supplementation with ActA enhances in vitro hESC differentiation toward germ cell lineage.
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